EZ-2053 in the Prophylaxis of Acute Pulmonary Allograft Rejection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Neovii Biotech
ClinicalTrials.gov Identifier:
NCT00105183
First received: March 8, 2005
Last updated: June 7, 2012
Last verified: June 2012
  Purpose

The purpose of this study is to assess the efficacy and safety of the study drug, known as "ATG Fresenius S," which is sometimes called "EZ-2053," to prevent a lung transplant patient's body from rejecting a transplanted lung or lungs.


Condition Intervention Phase
Chronic Obstructive Pulmonary
Idiopathic Pulmonary Fibrosis
Cystic Fibrosis
Bronchiectasis
Pulmonary Vascular Disease
Biological: Placebo
Biological: EZ-2053
Biological: EZ-2053 5mg/kg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Double-Blind, Placebo-Controlled, Multicenter, Dose-Ranging Study of an Anti-human-T-lymphocyte Immune Globulin (EZ-2053) in the Prophylaxis of Acute Pulmonary Allograft Rejection in Adult Recipients of Primary Pulmonary Allograft(s)

Resource links provided by NLM:


Further study details as provided by Neovii Biotech:

Primary Outcome Measures:
  • Number of Participants With the Event Death, Graft Loss, Acute Rejection and/or Loss to Follow-up (Whichever Occurred First) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of Participants With Death or Graft Loss Post-transplant [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Number of Participants With Acute Rejection [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Number of Participants With Infections and Infestations [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Number of Participants With Severe Adverse Events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Pulmonary Function Tests, Total Distance Walked 6 Minute Walk Test [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Pulmonary Function Test, Forced Vital Capacity [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Pulmonary Function Test, Forced Expiratory Volume in 1 Second [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Pulmonary Function Test, Forced Expiratory Flow 25-75 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 223
Study Start Date: January 2005
Study Completion Date: January 2011
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: EZ-2053
Anti-human-T-lymphocyte Immune Globulin, Rabbit (EZ-2053)
Biological: EZ-2053
single IV infusion, 9 mg/kg
Other Names:
  • ATG
  • Anti-human-T-Lymphocyte Immune Globulin, Rabbit
Placebo Comparator: Placebo
USP 0.9% sodium chloride solution
Biological: Placebo
placebo infusion, single
Other Name: Saline
Active Comparator: EZ-2053 5mg/kg
Anti-human-T-Lymphocyte Immune Globulin, Rabbit
Biological: EZ-2053 5mg/kg
single IV infusion, 5mg/kg
Other Names:
  • ATG
  • Anti-human-T-Lymphocyte Immune Globulin, Rabbit

Detailed Description:

Patients are generally consented for the study once they go on the lung transplant waiting list and then are re-consented periodically thereafter until they undergo the lung transplant surgery. A pre-surgical assessment consisting of medical history, physical exam, ECG, chest X-Ray, and blood tests are conducted. After lung transplant surgery, patients are assessed for continued eligibility. Within 6-24 hours after the end of surgery, patients are randomized to receive one infusion of study drug or placebo through a central venous catheter. Each day for 5 days following transplant surgery, patients are monitored for transplant rejection, infections, adverse events and laboratory test changes. On post-randomization Days 14, 30, 60, 90, 180, 270 and 365, patients will be monitored for acute transplant rejection, infections and cancer, pulmonary function tests and adverse experiences. Pulmonary biopsies will be performed on post-randomization Days 30, 60, 90, 180 and 365. Blood samples will be drawn during each visit.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recipient of a primary single or double pulmonary allograft
  • Capable of understanding the purposes and risks of the study and has given written informed consent, and agrees to comply with the study requirements
  • Women of childbearing potential must have a negative serum pregnancy test within 4 days prior to randomization.

Exclusion Criteria:

  • Undergoing second or living donor transplant
  • Prior treatment with T-cell depleting agents within the previous 5 years for the purpose of immunosuppression
  • Prior plasma exchange and/or treatment with IVIg within the past 5 years
  • Pulmonary infection with pan-resistant Pseudomonas or any Burkholderia species
  • Known positive blood cultures
  • Donor lung ischemia time > 8 hours for first lung and > 8 hours for the second lung
  • Previously received or is receiving a multi-organ transplant
  • Pregnant women, nursing mothers or women of child-bearing potential who are unwilling to use reliable contraception. Effective contraception must be used BEFORE beginning study drug therapy, for the duration of the study and for 6 months following completion of the study
  • Active, extra-pulmonary systemic infection requiring the prolonged or chronic use of antimicrobial agents or the presence of a chronic active hepatitis B or C
  • Active liver disease (liver function tests greater than or equal to 2 times the upper limit of normal)
  • Severe anemia (hemoglobin, < 6 g/dL), leukopenia (WBC < 2500/mm3), thrombocytopenia (platelet count < 80,000/mm3), polycythemia (Hct > 54% [male], Hct > 49% [female]) or clinically significant coagulopathy
  • Recipient or donor is seropositive for HIV
  • Previous exposure or known contraindication to administration of the study drug or to rabbit proteins
  • Current malignancy or a history of malignancy (within the previous 5 years), except non-metastatic basal cell or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix that has been treated successfully
  • Unstable cardiovascular disease, or a myocardial infarction within the previous 6 months
  • Currently participating in another clinical trial with an investigational agent and/or is taking or has been taking an investigational agent in the 30 days prior to transplant and/or has not recovered from any reversible side effects of prior investigational drug
  • Unlikely to comply with visits schedule in the protocol
  • Any current history of substance abuse, psychiatric disorder or a condition that, in the opinion of the Investigator, may invalidate communication with the Investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00105183

Locations
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
University of California, San Francisco
San Francisco, California, United States, 94143
Stanford University
Stanford, California, United States, 94305
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa Hospital & Clinics
Iowa City, Iowa, United States, 52242
United States, Kentucky
University of Kentucky Medical Center
Lexington, Kentucky, United States, 40536
United States, Missouri
Barnes-Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Oklahoma
INTEGRIS Baptist Medical Center
Oklahoma City, Oklahoma, United States, 73112
United States, Pennsylvania
University of Pennsylvania Medical Center
Philadelphia, Pennsylvania, United States, 19104
Temple University Hospital
Philadelphia, Pennsylvania, United States, 19140
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
University of Texas Health Sciences Center
San Antonio, Texas, United States, 78229
Australia, Victoria
The Alfred Hospital
Melbourne, Victoria, Australia
Austria
Medical University of Vienna
Vienna, Austria
Canada
University of Alberta
Edmonton, Alberta, Canada
Toronto General Hospital
Toronto, Canada
Sponsors and Collaborators
Neovii Biotech
Investigators
Principal Investigator: Elbert P Trulock III, MD Washington University School of Medicine
  More Information

No publications provided

Responsible Party: Neovii Biotech
ClinicalTrials.gov Identifier: NCT00105183     History of Changes
Other Study ID Numbers: EZ-2053-001
Study First Received: March 8, 2005
Results First Received: March 7, 2012
Last Updated: June 7, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Agency for Health and Food Safety

Keywords provided by Neovii Biotech:
pulmonary transplantation
Pulmonary Allograft Rejection

Additional relevant MeSH terms:
Bronchiectasis
Cystic Fibrosis
Fibrosis
Pulmonary Fibrosis
Vascular Diseases
Idiopathic Pulmonary Fibrosis
Bronchial Diseases
Respiratory Tract Diseases
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Cardiovascular Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial
Antilymphocyte Serum
Antibodies
Immunoglobulins
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014